This SBIR seeks to further the development of head pain treatment utilizing a newly emerging therapeutic delivery pathway to the trigeminal nerves and central nervous system - the final common pathway of most head and orofacial pain. The delivery pathway involves the intranasal administration of FDA approved analgesic peptides that are then transported directly to trigeminal pain targets, thus allowing for both delivery and targeting that was heretofore not attainable by standard routes due to obstacles of the GI/hepatic filters, blood borne enzymes, and the blood-brain barrier. The health implications of the proposal are its potential to mitigate the poorly treated morbidity of head and orofacial pain involving upwards of 45 million Americans. Using inflammatory temporomandibular joint pain as a model, the company seeks to explore the impact of analgesic peptides when delivered by this intranasal route. Specifically, the proposal seeks to explore the pharmacodynamics and pharmacokinetics of intranasally administered therapeutic peptides in order to demonstrate delivery, targeting and efficacy of the analgesic peptides at their targets in the central nervous system. Utilizing behavioral pain models and radiolabeled uptake and distribution studies, the company will assess the feasibility of these intranasal analgesic peptides for future human clinical testing. PUBLIC HEALTH RELEVANCE Orofacial and head pain represent one of the largest areas of morbidity in health care, involving upwards of 45 million Americans. One of the most prevalent and debilitating of these diseases is temporomandibular joint pain. Few options are available for those who suffer from these disorders, and disability as well as morbidity remains profound. This project explores a novel approach to treating this disorder by intranasally delivering appropriate drugs directly to their targets in the trigeminal nerves, brain and spinal cord, thus significantly increasing effectiveness while simultaneously reducing side effects.